tasquinimod

tasquinimod Property

Boiling point:

501.5±50.0 °C(Predicted)

Density 

1.427±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

insoluble in H2O; ≥20.32 mg/mL in DMSO; ≥4.75 mg/mL in EtOH with gentle warming and ultrasonic

form 

solid

pka

4.50±1.00(Predicted)

color 

White to light yellow

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

tasquinimod Chemical Properties,Usage,Production

Description

Tasquinimod is an orally-active quinoline-3-carboxamide derived from roquinimex, an immunomodulatory quinolone with applications in some cancers and autoimmune diseases. Tasquinimod inhibits tumor angiogenesis and supplements radiation or chemotherapy in animal models of prostate cancer. While its precise mechanism of action remains unclear, tasquinimod has been reported to alter signaling through S100A9, thrombospondin-1, HIF-1α, androgen receptor, VEGF, and HDAC3/4.

Uses

Tasquinimod is an orally active antiangiogenic agent which may inhibit HDAC4 signalling. This affects cancer cell survival thus making this compound and anti-cancer agent.

Synthesis

General procedure for Example 8 N-methyl-N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxoquinoline-3-carboxamide (Method B): 1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxoquinoline-3-carboxylic acid (8 g, 0.032 mol) and triethylamine ( 15.5 ml, 0.11 mol) were dissolved in 10 ml of dichloromethane and cooled to 0°C. Within 0.5 h, 150 ml of a dichloromethane solution of thionyl chloride (3.0 ml, 0.042 mol) was added dropwise to this solution while maintaining the temperature at 4°C. After the dropwise addition, stirring was continued at 4°C for 4 hours. After completion of the reaction, the reaction mixture was diluted with 10 ml of dichloromethane and washed sequentially with cold 1 M sulfuric acid and 1 M sodium hydroxide solution. The pH of the aqueous phase was adjusted to 8-8.5, clarified by filtration and acidified with hydrochloric acid to pH 4. Upon standing, a crystalline precipitate was formed, the precipitate was collected by filtration, washed with water and dried to afford the target product 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-(4-(trifluoromethyl)phenyl)-1,2-dihydroquinoline-3-carboxamide (8.5 g, 65% yield). The product was structurally confirmed by 1H NMR and 13C NMR and analyzed by ESI MS/MS.

in vivo

target

tumor microenvironment

IC 50

HDAC4: 10-30 nM (Kd)

storage

Store at -20°C

References

[1] Patent: US6133285, 2000, A
[2] Patent: EP1095021, 2003, B1. Location in patent: Page/Page column 9